POS0873 PERSISTENT INFLAMMATION IN SYSTEMIC SCLEROSIS IS STRONGLY ASSOCIATED WITH SEVERE DISEASE AND MORTALITY: AN ANALYSIS FROM THE EUSTAR DATABASE
Authors: A. C. Sarbu, S. Guler, O. Stadler, Y. Allanore, V. Bernardino, J. H. W. Distler, A. Gabrielli, A. M. Hoffmann-Vold, M. Matucci-Cerinic, U. Müller-Ladner, V. Ortiz-Santamaria, S. Rednic, V. Riccieri, V. Smith, S. Ullman, U. Walker, T. Geiser, O. Distler, B. Maurer, F. Kollert
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) is a heterogeneous autoimmune disease, with a high disease-related mortality and morbidity. A subset of patients show elevated CRP levels (20-35%), which has been reported as inflammatory SSc. Preliminary data suggest that this subset is characterized by a severe phenotype. Objectives To analyse the phenotype and the survival of inflammatory compared with non-inflammatory SSc patient subsets. Methods Data from 8571 SSc patients with available CRP measurement from the EUSTAR cohort were analysed. Exclusion criteria included acute infection, missing follow-up and tocilizumab treatment. Patients with a CRP ≥5mg/l at ≥80% of visits were stratified as persistent inflammatory and as non-inflammatory if CRP was ≥5 mg/l at &lt;20% of visits (as described previously (1)). As a sensitivity analysis, patients were defined as inflammatory and non-inflammatory based on a single CRP measurement at baseline only (CRP ≥5 or &lt;5mg/l, respectively). We compared baseline characteristics using Chi-square and non-parametric Kruskal–Wallis tests as appropriate. Kaplan Meier curves with log-rank tests were used to estimate time from baseline to death or censoring, and Cox regression to compare mortality risks adjusted for time from diagnosis to baseline. Results Out of 2883 patients with more than two visits, 404 (14%) showed persistent inflammation and 1032 (36%) a non-inflammatory phenotype. Out of 5619 patients with more than one visit, 1830 (33%) were stratified as inflammatory as defined by as single CRP measurement at baseline and 3789 (67%) as non-inflammatory. With both definitions, the inflammatory subset revealed a more severe phenotype than non-inflammatory patients, including more frequent diffuse-cutaneous disease, anti-Scl-70 autoantibodies, pulmonary fibrosis, pulmonary hypertension, higher modified Rodnan skin score, and lower forced vital capacity and diffusing capacity for carbon monoxide. Patients with persistent inflammation had a strongly increased risk of all-cause mortality (HR 7.1 [95%CI 3.7 to 13.5], p&lt;0.001) compared to non-inflammatory patients, whereas this association was weaker when based on a single CRP measurement (HR 2.6 [95%CI 2.1 to 3.2], p&lt;0.001). Conclusion The severe phenotype and decreased survival of the inflammatory SSc subset, which was most prominent in patients with persistently elevated CRP levels, suggest a distinct disease subset. Therefore both, the need for more regular monitoring of inflammatory parameters and implications for immune-modulating treatment, needs to be carefully analysed. References [1]Mitev, A., et al., Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide. Arthritis Res Ther, 2019. 21(1): p. 262. PMID: 31791379 Figure 1. Overall mortality from baseline onward a. by persistent inflammatory phenotype, b. by inflammatory phenotype at baseline Disclosure of Interests Adela-Cristina Sarbu: None declared, Sabina Guler: None declared, Odile Stadler: None declared, Yannick Allanore: None declared, Vera Bernardino: None declared, Jörg H.W. Distler: None declared, Armando Gabrielli: None declared, Anna-Maria Hoffmann-Vold: None declared, Marco Matucci-Cerinic: None declared, Ulf Müller-Ladner: None declared, Vera Ortiz-Santamaria: None declared, Simona Rednic: None declared, Valeria Riccieri: None declared, Vanessa Smith: None declared, Susanne Ullman: None declared, Ulrich Walker: None declared, Thomas Geiser: None declared, Oliver Distler: None declared, Britta Maurer Speakers bureau: Boehringer-Ingelheim, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, Grant/research support from: AbbVie, Protagen, Novartis Biomedical Research, Florian Kollert Shareholder of: Roche, Consultant of: BMS, Actelion, Boehringer-Ingelheim, Pfizer, Grant/research support from: Roche, Gilead, Pfizer, Employee of: Roche